Twenty-four-month alpha-galactosidase A replacement therapy in Fabry disease has only minimal effects on symptoms and cardiovascular parameters.

Fabry disease is an X-linked lysosomal storage disease caused by deficiency of alpha-galactosidase A enzyme activity. Decreased enzyme activity leads to accumulation of glycosphingolipids in different tissues including endothelial cells and smooth-muscle cells and cardiomyocytes, and cardiovascular complications are common in the disease. Since 2001, specific enzyme replacement therapy (ERT) with alpha-galactosidase A has been available. It has been reported to improve clinical symptoms and quality of life. However, limited and controversial data on its efficacy to cardiac involvement have been published. Nine patients (5 male) with Fabry disease were included in an open-label prospective follow-up study of 24-month ERT. Comprehensive cardiovascular evaluation was performed by MRI, stress echocardiography and quality of life assessment. Plasma globotriaosylceramide decreased from 6.2 to 1.4 microg/ml during ERT (p<0.05). The only other measured parameters that changed significantly were resting heart rate that decreased from 79 to 67 bpm (p<0.01) and end-systolic volume that decreased by 12.4 ml (p<0.05). The other parameters consisting of quality of life, self-estimated cardiovascular condition, diastolic function, exercise capacity, ECG parameters, ejection fraction and ventricular mass did not change. ERT has only minimal effect on symptoms and cardiovascular morphology and function in Fabry disease. Therefore, effective conventional medical therapy is still of major importance in Fabry disease. Larger ERT studies are warranted, especially in women, to solve current open questions, such as the age at which ERT should be started, optimal dosage and intervals between infusions. Furthermore, longer follow-up studies are needed to assess the effects of ERT on prognosis.

Correlation of transthoracic Doppler echocardiography and magnetic resonance imaging in measuring left anterior descending artery flow velocity and time-course of dipyridamole-induced coronary flow increase.

There is an increasing need for new, functional and more quantitative parameters to assess coronary arterial function, for the purposes of evidence-based medicine. Coronary arterial function has been widely studied using pharmacological stimulation induced by dipyridamole or adenosine. Coronary flow reserve (CFR), defined as the ratio of pharmacologically induced hyperemic flow divided by basal flow, has been found to be an important functional index in both the clinical and subclinical stages of cardiovascular diseases. Ten healthy male volunteers were studied to compare transthoracic Doppler echocardiography (TTE) and MRI for measuring left anterior descending coronary artery (LAD) flow velocity and CFR. Additionally, the time-response curve of dipyridamole infusion was studied in five healthy males using TTE. Assessment of blood flow velocity, measured as MDV, PDV and VTI indicated Pearson's correlation coefficients of 0.88, 0.85 and 0.70, respectively, between flow velocity measurements performed using TTE and MRI. The results indicate that, despite minor differences in LAD diastolic velocities measured by TTE and MRI, the correlation of the LAD diastolic velocities measured using both methods are good and both methods are feasible for measuring CFR. Moreover, TTE has the unique capability of continuous measurement of LAD flow velocity, which allowed assessment of the time-response curve for dipyridamole-induced increase in LAD flow velocity in this study. This study indicates that the TTE method may be used in sequential or on-line monitoring of LAD blood flow velocity and therefore can be applied to evaluate the time- or dose-response effects of infused drugs in the coronary circulation of humans.

Decreased large artery distensibility in borderline hypertension is related to increased in vivo low-density lipoprotein oxidation.

The present study tested the hypothesis that reduced arterial elasticity seen in hypertension is related to increased oxidation of LDL. Fifteen men with borderline hypertension (BHT), with blood pressure values classified as high normal (systolic blood pressure 130-140 mmHg or diastolic blood pressure 85-89 mmHg) were included. The control group comprised 22 men with normal blood pressure values (<135/80 mmHg) matched for age, body size and LDL-cholesterol level. Distensibility of aorta was measured using magnetic resonance imaging, and distensibility of the common carotid artery using ultrasound. Baseline LDL diene conjugation was used as a marker for ox-LDL. Aortic and carotid distensibilities were lower in the BHT men than in controls (1.4 +/- 0.6 vs. 1.9 +/- 0.6%/10 mmHg, p<0.05 for aortic distensibility; 2.9 +/- 0.9 vs. 3.6 +/- 0.6%/10 mmHg, p<0.05 for carotid distensibility). Ox-LDL was significantly higher in the BHT men than in controls (44 +/-15 vs. 28 +/- 8 micromol/L, p<0.01). In univariate analysis, ox-LDL associated with aortic distensibility (r=-0.43, p<0.05). In multivariate analysis, the differences in distensibilities between the groups disappeared when the values were adjusted for ox-LDL. These data show decreased arterial elasticity and increased LDL oxidation in young men with borderline hypertension, and suggest that oxidative modification of LDL particles may play a pathophysiological role in the development of reduced arterial distensibility in hypertension.

Ambulatory blood pressure characteristics in normotensive and treated hypertensive older people.

The objective of this study was to determine the normal values and characteristics of 24-h ambulatory blood pressure (ABP) and to describe the ABP level of treated hypertensive subjects in an older Finnish population. ABP was measured in 502 randomly selected subjects aged 64 years or over living in a Finnish municipality (mean age 70 years, range 64-87 years). A total of 211 subjects did not have blood pressure (BP) affecting medication. ABP measurements were taken every 30 min for 24 h, and the day- and night-time periods were diary-based. The results were that in untreated subjects, the average office BP was 134/82 +/- 16/9 (s.d.) mm Hg for men and 140/81 +/- 18/8 mm Hg for women. The 24-h average BP was 120/75 +/- 14/8 mm Hg (95th percentile upper limit 145/93 mm Hg) for men and 125/75 +/- 15/7 (95th = 154/89 mm Hg) for women. The daytime averages were 127/78 +/- 12/7 mm Hg (95th = 154/99 mm Hg) and 131/78 +/- 15/7 mm Hg (95th = 158/91 mm Hg) for men and women, respectively. The ABP daytime value of 130/83 mm Hg corresponded best to the office BP value of 140/90 mm Hg. All BP values were significantly higher in the treated hypertensive group compared to the normotensive group. Night-time BP was markedly lower than daytime BP, and no difference in circadian variability was found between the normotensive and hypertensive subjects. Both office and ambulatory BPs were significantly higher in women than in men. This study provides sex-specific normal values for ABP in a 64 to 87-year-old age group. The normal values of ABP were markedly lower than the office BP values. Hypertensives, even when treated, tended to have elevated values.

Ambulatory blood pressure and left ventricular mass in older age.

BACKGROUND: The purpose of this study was to analyse the association of ambulatory blood pressure (ABP) to left ventricular mass (LVM) in a population aged over 64 years and to describe the level of ABP in subjects with and without left ventricular hypertrophy (LVH) in older age. METHODS: ABP measurement and echocardiography for calculation of LVM were assessed in 490 inhabitants (mean age 70.7 years, range 64-87 years) of a small town in southwestern Finland who were able to visit an outpatient clinic. Explanatory factors associated with LVM were assessed with linear regression analysis. LVH was defined as calculated LVM-index values exceeding 150 g/m2 in men and 120 g/m2 in women adopted from the Framingham Study. RESULTS: Systolic ABP was significantly associated with LVM. No correlation between diastolic ABP and LVM was found. Other factors independently related to LVM were gender, body mass index and age. The prevalence of echocardiographic LVH was 22%. Subjects with LVH had markedly higher systolic ABP levels than those without LVH (mean (SD) 24-h ABP: 132(16)/75(8) mmHg vs. 123(13)/75(8) mmHg). CONCLUSION: Systolic ABP is associated with LVM in older people. In addition, systolic ABP is superior to diastolic ABP in relation to LVM in the aged.

Increased aortic intima-media thickness: a marker of preclinical atherosclerosis in high-risk children.

BACKGROUND: Autopsy studies in children have shown that atherosclerotic lesions begin to develop first in the intima of the aorta. Recent developments in ultrasound techniques have made it possible to visualize the intima-medial thickness of the abdominal aorta directly (aIMT). Therefore, we examined the feasibility of measuring aIMT in children and studied its value in distinguishing high-risk children from healthy controls compared with a more established marker of subclinical atherosclerosis, the common carotid artery intima-medial thickness (cIMT). METHODS AND RESULTS: IMTs were measured using high-resolution (13 MHz) ultrasound in 88 children (aged 11+/-2 years); 16 had hypercholesterolemia (LDL cholesterol, 5.1+/-1.2 mmol/L), 44 had type 1 diabetes (mean duration, 4.4+/-3.1 years; LDL cholesterol, 2.3+/-0.7 mmol/L), and 28 were healthy (controls; LDL cholesterol, 2.5+/-0.8 mmol/L). High-risk children had significantly increased aIMTs and cIMTs (both P<0.001) compared with controls. In controls, aIMT was similar to cIMT (P=NS), but aIMT was higher than cIMT in the children with hypercholesterolemia and diabetes (both P<0.01). Both markers showed excellent and approximately equal between-observer (<4%) and between-subject variation (<5%). CONCLUSIONS: Children with hypercholesterolemia and diabetes show increased IMTs compared with healthy controls, with a relatively greater increase in the aIMT than in the cIMT. Because atherosclerosis begins first in the intima of the aorta, these data suggest that the aIMT might provide the best currently available noninvasive marker of preclinical atherosclerosis in children.

Assessing coronary sinus blood flow in patients with coronary artery disease: a comparison of phase-contrast MR imaging with positron emission tomography.

OBJECTIVE: This study was performed to determine whether MR imaging can be used to reliably measure global myocardial blood flow and coronary flow reserve in patients with coronary artery disease as compared with such measurements obtained by positron emission tomography (PET). SUBJECTS AND METHODS: We measured myocardial blood flow first at baseline and then after dipyridamole-induced hyperemia in 20 patients with coronary artery disease. Myocardial blood flow as revealed by MR imaging was calculated by dividing coronary sinus flow by the left ventricular mass. Coronary flow reserve was calculated by dividing the rate of hyperemic flow by the rate of baseline flow. RESULTS: Using MR imaging, myocardial blood flow at baseline was 0.73 +/- 0.23 mL x min(-1) x g(-1), and at hyperemia the blood flow was 1.43 +/- 0.37 mL x min(-1) x g(-1), yielding an average coronary flow reserve of 1.99 +/- 0.47. Using PET, myocardial blood flow was 0.89 +/- 0.21 mL x min(-1) x g(-1) at baseline and 1.56 +/- 0.42 mL x min(-1) x g(-1) at hyperemia, yielding an average coronary flow reserve of 1.77 +/- 0.36. The correlation of myocardial blood flow and coronary flow reserve measurements for these two methods was an r of 0.80 (p < 0.01) and an r of 0.50 (p < 0.05), respectively. CONCLUSION: This study shows that myocardial blood flow measurements obtained using MR imaging have a good correlation with corresponding PET measurements. Coronary flow reserve measurements obtained using MR imaging had only moderate correlation with PET-obtained measurements. Our results suggest that MR imaging flow quantification could potentially be used for measuring global myocardial blood flow in patients in whom interventional treatment for coronary artery disease is being evaluated.

Global myocardial blood flow and global flow reserve measurements by MRI and PET are comparable.

Coronary flow reserve (CFR) measurements have been widely used in assessing the functional significance of coronary artery stenosis because they are more sensitive in predicting major cardiac events than angiographically detected reductions of coronary arteries. Myocardial blood flow can be determined by measuring coronary sinus (CS) flow with velocity-encoded cine magnetic resonance imaging (VEC-MRI). The purpose of this study was to compare global myocardial blood flow (MBF) and CFR measured using VEC-MRI with MBF and CFR measured using positron emission tomography (PET). We measured MBF at baseline and after dipyridamole-induced hyperemia in 12 male volunteers with VEC-MRI and PET. With VEC-MRI, MBF was 0.64 +/- 0.09 (ml/min/g) at baseline and 1.59 +/- 0.79 (ml/min/g) at hyperemia, which yielded an average CFR of 2.51 +/- 1.29. With PET, MBF was 0.65 +/- 0.20 (ml/min/g) at baseline and 1.78 +/- 0.72 (ml/min/g) at hyperemia, which yielded an average CFR of 2.79 +/- 0.97. The correlation of MBFs between these two methods was good (r = 0.82, P < 0.001). The CFRs measured by MRI correlated well with those measured using PET (r = 0.76, P < 0.004). These results suggest that MRI is a useful and accurate method to measure global MBF and CFR. Therefore, it would be suitable for studying risk factor modifications of vascular function at an early stage in healthy volunteers.

Noninvasive assessment of brachial artery endothelial function with digital ultrasound and 13-MHz scanning frequency: feasibility of measuring the true inner luminal diameter using the intima-lumen interface.

Previous studies assessing endothelial function as flow-mediated changes in the brachial artery diameter have not been able to measure the true inner luminal diameter. This is due to the lack of image quality, which has hampered the visualisation of the lumen-intimal interface. Because increases in resolution and scanning frequency have recently led to improved ultrasound (US) image quality, we assessed the feasibility of measuring the true brachial artery diameter using digital US and 13-MHz scanning frequency. Satisfactory true inner diameter measurements were obtained in all subjects (n = 148, middle-aged men, mean age 54 +/- 7 y) participating in a risk factor study. At baseline flow, the intima to intima diameter was 4.03 +/- 0.49 and 4.67 +/- 0.52 mm measured conventionally from the anterior to the posterior media-adventitia interface (difference 0.64 +/- 0.10 mm). After hyperaemia, the intima to intima diameter was 4.23 +/- 0.46 mm and the adventitia to adventitia diameter 4.86 +/- 0.50 mm. Flow-mediated dilation (FMD) expressed as the percentage change from the baseline diameter measured 5.3 +/- 4.3% using the true inner diameters and 4.3 +/- 3.7% using the conventional outer diameters. The difference in FMD values was systematic, and there was a good linear correlation between them (r = 0.93, p < 0.0001). If FMD is presented as the percentage change from baseline to hyperaemia, this new method gives values that are approximately 1% unit higher, compared with values when brachial luminal diameter is measured in the conventional way between the adventitia-media interfaces.

Technical achievement: transthoracic Doppler echocardiography can be used to detect LAD restenosis after coronary angioplasty.

We investigated the capability of transthoracic Doppler echocardiography (TTE) to detect and quantify the severity of restenosis in the left anterior descending coronary artery (LAD) after percutaneous transluminal coronary angioplasty (PTCA). We studied 10 consecutive patients assigned for quantitative coronary angiography (qCA) due to a recurrent angina pectoris after PTCA of the LAD. The LAD was visualized by TTE, and the presence of local turbulence and an increase in the blood flow velocity was regarded to indicate coronary stenosis. To assess the severity of the stenosis, the increase of blood flow velocity was measured. Angiography showed stenoses of various degrees (27-100%) in all patients. All stenoses were detectable using TTE. Moreover, the ratio of maximal blood flow velocity at the site of stenosis to the pre-stenotic blood flow velocity (M/P-ratio) correlated significantly with the reduction of the luminal diameter of LAD (r = 0.85, P < 0.003). A M/P-ratio higher than 3.0 predicted a diameter reduction of 50% or higher with sensitivity and specificity of 100% in patients with a subtotal stenosis (n = 9). Our results indicate that stenoses in the LAD could be found and the severity of the stenoses could be quantified reliably with TTE. This approach is totally non-invasive and less expensive than coronary angiography and can be used clinically in clarifying restenosis after coronary angioplasty.

Assessment of coronary flow reserve using fast velocity-encoded cine MR imaging: validation study using positron emission tomography.

OBJECTIVE: Previous studies using intravascular Doppler sonography and positron emission tomography (PET) have shown that the hemodynamic significance of coronary artery stenosis can be evaluated by measuring coronary flow reserve. The purpose of this study was to assess whether MR imaging measurements of coronary flow reserve in the left anterior descending artery are comparable with those obtained with PET in the corresponding territory. SUBJECTS AND METHODS: MR imaging and PET flow measurements were obtained in 10 healthy volunteers. Blood flow velocity in the left anterior descending artery was measured with breath-hold velocity-encoded cine MR imaging before and after IV administration of dipyridamole. The coronary flow velocity reserve measured by MR imaging was compared with the myocardial perfusion reserve in the anterior myocardium quantified on using PET and (15)O-labeled water. RESULTS: The average flow velocity reserve in the left anterior descending artery measured on MR imaging was 2.44+/-1.14 in healthy volunteers, which was comparable with the myocardial perfusion reserve measured by PET (2.52+/-0.84). MR imaging and PET measurements of the coronary flow reserve showed a significant correlation (r = 0.79, p<0.01). CONCLUSION: MR imaging measurement of the flow velocity reserve in the proximal left anterior descending artery correlates well with the myocardial perfusion reserve obtained with PET and (15)O-labeled water.

Increased arterial intima-media thickness and in vivo LDL oxidation in young men with borderline hypertension.

We used borderline hypertension as a model for prehypertension to examine the early influences of elevated blood pressure on subclinical atherosclerosis, lipoprotein oxidation, and cardiac adaptation. Healthy men (age 37+/-4 years) were classified prospectively into 2 groups on the basis of having either borderline hypertension (systolic 130 to 140 mm Hg or diastolic 85 to 89 mm Hg, n=16) or normal (<130/85 mm Hg, n=22) blood pressure values during the previous 2 years. The groups were matched for age, body size, and serum cholesterol levels. High-resolution ultrasound was used to measure intima-media thickness (IMT) of the carotid and brachial arteries, cardiac dimensions, and brachial artery endothelial function. Baseline low-density lipoprotein (LDL)-diene conjugation was measured as an estimate of in vivo LDL oxidation (ox-LDL). Compared with normotensive controls, men with borderline hypertension had higher IMT of the carotid artery (0.58+/-0.06 versus 0.75+/-0.07 mm, P<0.001) and IMT of the brachial artery (0.45+/-0.05 versus 0.57+/-0.07 mm, P<0.001), and increased levels of ox-LDL (29+/-9 versus 47+/-17 mol/L, P<0.001), but similar endothelial function. Left ventricular mass was similar in both groups, but there were significant differences in left ventricular geometry. In multivariate analyses, the predictors of carotid IMT were 24-hour systolic blood pressure (P<0.001) and ox-LDL (P=0.10). The current study demonstrates evidence of increased subclinical atherosclerosis and ox-LDL in borderline hypertension. These results are consistent with the idea that enhanced ox-LDL may be one of the pathophysiological events related to development of atherosclerosis in men with borderline elevated blood pressure.

HMG CoA reductase inhibitors are related to improved systemic endothelial function in coronary artery disease.

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase (statins) may enhance vascular endothelial function independent of their cholesterol lowering effect. To test this hypothesis, we surveyed two groups of patients (age 55+/-7, mean+/-SD) with coronary artery disease that were matched for age, blood pressure and serum lipid levels. Group 1 comprised 23 men without lipid-lowering medication and Group 2 included 22 patients with ongoing HMG CoA reductase inhibitor medication. Flow-mediated (endothelium-dependent) arterial dilatation (FMD) and nitrate-mediated (smooth muscle dependent) dilatation (NMD) were measured in the brachial artery using high resolution ultrasound. FMD was considerably higher in group 2 (4.3+/-2.6 vs. 2.6+/-2.8%; P<0.05). In multivariate regression model, statin use was the only significant (P<0.05) predictor of FMD. In all subjects, FMD correlated with statin dose (P<0.05 for trend). NMD was non-significantly higher in group 2 (11.4+/-5.0 vs. 9.0+/-4.2%, P=0. 08). We conclude that patients with established coronary artery disease on HMG CoA reductase inhibitor therapy have better vascular endothelial function than similar patients without the medication. These data provide further support for the idea that HMG CoA reductase inhibitors enhance endothelial function independent of their lipid-lowering effects. This may suggest that these drugs could be beneficial in secondary prevention of coronary artery disease regardless of the serum cholesterol concentration.

Constantly low HDL-cholesterol concentration relates to endothelial dysfunction and increased in vivo LDL-oxidation in healthy young men.

To test the hypothesis that low HDL-C concentration interferes with vascular endothelial function and lipoprotein oxidation, we measured endothelium-dependent flow mediated dilatation (FMD, %) of the brachial artery in young men (n=20) classified prospectively into two groups on basis of having either low or high HDL-C concentration over the past 2 years. As an estimate of in vivo low-density lipoprotein oxidation (ox-LDL), we measured LDL diene conjugation. FMD was present in the group with high HDL-C concentration, but impaired in the group with low HDL-C (5.5+/-3.2 vs 0.2+/-1.2%, P<0. 001). The group with high HDL-C level had significantly lower levels of ox-LDL compared to low HDL-C group (18.0+/-1.8 vs 22.9+/-4.4, P

Large-artery elastic properties in young men : relationships to serum lipoproteins and oxidized low-density lipoproteins.

Measures of arterial elasticity have been proposed as surrogate markers for asymptomatic atherosclerosis. We investigated the relations of serum lipoproteins, oxidized low-density lipoprotein (ox-LDL), and familial hypercholesterolemia (FH) to arterial elasticity among young men. As a marker of arterial elasticity we measured compliance in the thoracic aorta by using magnetic resonance imaging and in the common carotid artery by using ultrasound. LDL diene conjugation was used as a marker of ox-LDL. In study I, 25 healthy men (aged 29 to 39) were classified into 2 extreme groups according to previously measured high-density lipoprotein cholesterol to total cholesterol ratio (HDL-C/TC ratio). In study II, the healthy men were used as controls for 10 age matched asymptomatic patients with FH. In healthy men, the group with low HDL-C/TC ratio had decreased carotid artery compliance (2. 3+/-0.4% versus 1.9+/-0.5%/10 mm Hg, P=0.034). In univariate analysis, the compliance of the carotid artery associated with ox-LDL (r =-0.49, P=0.016) and HDL-C/TC ratio (r=0.41, P=0.040). In multivariate regression analyses, ox-LDL was the only independent determinant for compliance of the carotid artery (P=0.016). Aortic elasticity was not related to standard lipid variables, but the compliance of the ascending aorta associated with ox-LDL (r=-0.44, P=0.030). In FH patients, arterial elasticity was similar to that in controls. We conclude that elasticity of the common carotid artery is affected by serum lipid profile in young men. The current study demonstrates for the first time an in vivo association between ox-LDL and arterial elasticity suggesting that oxidative modification of LDL may play a role in the alteration of arterial wall elastic properties.

Diagnosis of infective endocarditis. Sensitivity of the Duke vs von Reyn criteria.

BACKGROUND: Because of the highly variable clinical manifestations of infective endocarditis (IE), different sets of diagnostic criteria have been used to standardize case definitions of IE. We evaluated the validity of the recently proposed Duke criteria, as compared with the older von Reyn criteria, in patients with no history of injecting drug abuse. METHODS: A total of 243 consecutive episodes of suspected IE in 222 patients treated during the years 1980 through 1995 in a Finnish teaching hospital were retrospectively evaluated for the likelihood of IE by means of these 2 classification schemes. RESULTS: Of all disease episodes, 114 were designated as definite IE by the Duke criteria, as compared with 64 episodes so classified by the von Reyn criteria (P < .001; Fisher exact test). Moreover, as many as 115 disease episodes were rejected by the von Reyn criteria, whereas only 37 episodes were rejected by the Duke criteria (P < .001). Of the cases rejected by the von Reyn criteria, the Duke clinical criteria designated 6 (5%) as definite IE and 72 (63%) as possible IE. Among histopathologically verified episodes, 46 were designated as definite IE by the Duke clinical criteria, as compared with a diagnosis of probable IE by the von Reyn criteria in 33 episodes (P = .02). Moreover, 26 pathologically proved cases would have been rejected by the von Reyn criteria had surgery not been performed, as compared with none being rejected by the Duke criteria (P < .001). CONCLUSIONS: Corroborating earlier findings, the higher sensitivity of the Duke criteria, as compared with the von Reyn criteria, was demonstrated in this study. These results confirm the validity of the Duke criteria in diagnosing IE in a non-drug-addict patient population.

Evaluation of left atrial contribution to left ventricular filling in aortic stenosis by velocity-encoded cine MRI.

Velocity-encoded cine MRI (VEC-MRI) can measure volume flow at specified site in the heart. This study used VEC-MRI to measure flow across the mitral valve to compare the contribution of atrial systole to left atrial filling in normal subjects and patients with left ventricular hypertrophy. The study population consisted of 12 normal subjects (mean age 34.5 years) and nine patients with various degrees of left ventricular hypertrophy resulting from aortic stenosis (mean age 70 years). VEC-MRI was performed in double-oblique planes through the heart to measure both the mitral inflow velocity pattern (E/A ratio) and the volumetric flow across the mitral valve. The left atrial contribution to left ventricular filling (AC%) was calculated. The results were compared with Doppler echocardiographic parameters. The VEC-MRI-derived mitral E/A ratios showed a significant linear correlation with E/A ratios calculated from Doppler echocardiography (r = 0.94), and the VEC-MRI-derived E/A ratios (2.1 +/- 0.5 vs 1.0 +/- 0.4) and AC% values (24.9 +/- 7.2 vs 45.7 +/- 16.4) were significantly different between normal subjects and patients with aortic stenosis (p < 0.01 in both groups). The same differences were seen in the Doppler echocardiographic parameters. The VEC-MRI-derived E/A ratio and AC% showed significant hyperbolic and linear correlations with left ventricular mass indexes (r = 0.95 and 0.86). In addition, the VEC-MRI-determined E/A ratio and the volumetric AC% displayed a highly significant hyperbolic correlation (r = 0.95). Thus VEC-MRI can be used to evaluate left ventricular diastolic filling characteristics in normal subjects and patients with abnormalities of diastolic filling.

Quantification of mitral regurgitation by velocity-encoded cine nuclear magnetic resonance imaging.

OBJECTIVES: The feasibility of velocity-encoded cine nuclear magnetic resonance (NMR) imaging to measure regurgitant volume and regurgitant fraction in patients with mitral regurgitation was evaluated. BACKGROUND: Velocity-encoded cine NMR imaging has been reported to provide accurate measurement of the volume of blood flow in the ascending aorta and through the mitral annulus. Therefore, we hypothesized that the difference between mitral inflow and aortic systolic flow provides the regurgitant volume in the setting of mitral regurgitation. METHODS: Using velocity-encoded cine NMR imaging at a magnet field strength of 1.5 T and color Doppler echocardiography, 19 patients with isolated mitral regurgitation and 10 normal subjects were studied. Velocity-encoded cine NMR images were acquired in the short-axis plane of the ascending aorta and from the short-axis plane of the left ventricle at the level of the mitral annulus. Two independent observers measured the ascending aortic flow volume and left ventricular inflow volume to calculate the regurgitant volume as the difference between left ventricular inflow volume and aortic flow volume, and the regurgitant fraction was calculated. Using accepted criteria of color flow Doppler imaging and spectral analysis, the severity of mitral regurgitation was qualitatively graded as mild, moderate or severe and compared with regurgitant volume and regurgitant fraction, as determined by velocity-encoded cine NMR imaging. RESULTS: In normal subjects the regurgitant volume was -6 +/- 345 ml/min (mean +/- SD). In patients with mild, moderate and severe mitral regurgitation, the regurgitant volume was 156 +/- 203, 1,384 +/- 437 and 4,763 +/- 2,449 ml/min, respectively. In normal subjects the regurgitant fraction was 0.7 +/- 6.1%. In patients with mild, moderate and severe mitral regurgitation, the regurgitant fraction was 3.1 +/- 3.4%, 24.5 +/- 8.9% and 48.6 +/- 7.6%, respectively. The regurgitant fraction correlated well with the echocardiographic severity of mitral regurgitation (r = 0.87). Interobserver reproducibilities for regurgitant volume and regurgitant fraction were excellent (r = 0.99, SEE = 238 ml; r = 0.98, SEE = 4.1%, respectively). CONCLUSIONS: These findings suggest that velocity-encoded NMR imaging can be used to estimate regurgitant volume and regurgitant fraction in patients with mitral regurgitation and can discriminate patients with moderate or severe mitral regurgitation from normal subjects and patients with mild regurgitation. It may be useful for monitoring the effect of therapy intended to reduce the severity of mitral regurgitation.

Velocity-encoded cine MRI in the evaluation of left ventricular diastolic function: measurement of mitral valve and pulmonary vein flow velocities and flow volume across the mitral valve.

Left ventricular diastolic function has been evaluated by means of analysis of the flow pattern through the mitral valve. Velocity-encoded cine magnetic resonance imaging (VEC-MR) is a new method for characterizing flow patterns in the heart. The feasibility of using VEC-MR to measure early diastolic (E) and atrial systolic (A) peak flow velocities and E/A ratios in the mitral inflow, as well as systolic (X), early diastolic (Y), and atrial systolic (Z) peak flow velocities and X/Y ratios in the pulmonary vein, was evaluated in 10 normal volunteers. The VEC-MR-derived velocities and indexes were compared with Doppler-derived results. Volumetric flow across the mitral valve was also used to measure stroke volume, cardiac output, and the left atrial contribution of left ventricular filling. VEC-MR yielded lower peak velocities than Doppler echocardiography. The velocities of the two measurements showed a significant linear correlation (Doppler E velocity = 1.30 x VEC-MR + 1.6 cm/sec, r = 0.68; Doppler A velocity = 1.83 x VEC-MR - 5.2 cm/sec, r = 0.83; and Doppler X velocity = 0.45 x VEC-MR + 0.09 cm/sec, r = 0.74). Consequently the E/A and X/Y ratios measured by these two methods showed statistically significant linear correlations with r values of 0.94 and 0.83. The volume of blood flow across the mitral valve measured by VEC-MR (5610 +/- 620 ml/min) was not statistically different from the cardiac output measured from the ascending aorta by VEC-MR (5670 +/- 590 ml/min) or by left ventricular cine magnetic resonance imaging (5440 +/- 614 ml/min). The left atrial contribution to left ventricular filling was 25.9 +/- 7.5%. Our results indicate that VEC-MR can be used not only for evaluation of left ventricular diastolic filling from the mitral valve and pulmonary vein flow velocities but also for quantitative measurement of the volume of blood flow across the mitral valve.

Right ventricular diastolic filling: evaluation with velocity-encoded cine MRI.

Abnormal flow velocity curves across the tricuspid valve (TV) and in the superior vena cava have been described in patients with abnormal right ventricular (RV) relaxation or restriction and with pericardial diseases by means of Doppler echocardiography. In this study, various imaging planes and strategies of velocity-encoded cine (VEC) MR for measurement of peak E and peak A velocities and the E/A ratio across the TV were evaluated and compared to Doppler measurements in 10 normal volunteers. In addition, VEC-MR velocity measurements were performed in the superior vena cava. Peak E and peak A velocities derived from three-dimensional VEC-MR phase images were slightly higher than velocities derived from two-dimensional VEC images. Higher velocities were measured by VEC-MR in the vertical long-axis plane compared with the horizontal long-axis plane. Excellent correlations (r > 0.89) were found between E/A ratios derived by VEC-MR and Doppler echocardiography. The interobserver variability for VEC-MR measurements was in the range of 2%. The VEC-MR depicted normal superior vena cava velocity curves in every volunteer. These results indicate that VEC-MR may offer a highly reproducible means of assessing abnormal filling properties of the RV.